IGF-1 DES, written in research papers as des(1-3)IGF-I, is a shortened form of insulin-like growth factor 1 (IGF-1) that is missing the first three amino acids of the chain. It occurs naturally: it was isolated from human brain in 1986 and from cow colostrum (the first milk after birth) in 1988. In laboratory work it is roughly 10 times more potent than full-length IGF-1, because it barely sticks to the IGF binding proteins that normally hold IGF-1 in check (Ballard et al., Int J Biochem Cell Biol 1996).
The single most important fact is that IGF-1 DES has never been tested in a controlled human trial and has never been approved as a medicine anywhere. Everything known about its effects comes from cell culture and animal studies, mostly in rats, from the late 1980s and 1990s. It is sold online as a research chemical and is banned in sport (Mongongu et al., Drug Test Anal 2021).
This page summarizes what laboratory studies, animal research and regulators report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Class | Peptide growth factor; naturally occurring truncated variant of IGF-1 |
| Also called | des(1-3)IGF-I, des-IGF-1, destripeptide IGF-1, IGF-1 DES |
| Structure | Human IGF-1 lacking its first three amino acids (glycine–proline–glutamate) |
| Approval status | Never approved for human use; no controlled human trials |
| Potency in cell culture | About 7–10 times IGF-1 at stimulating protein synthesis in rat muscle cells |
| Key mechanism fact | Binds the IGF-1 receptor about as well as IGF-1, but binds IGF binding proteins very weakly |
| Half-life | No published value in humans or animals; in rats, plasma clearance was 4.59 vs 1.20 mL/min/kg for IGF-1 |
| US status | Not FDA-approved; not on the DEA Schedule III list |
| WADA status | Prohibited at all times (S2.3, IGF-1 and its analogues) |
What it is
Full-length IGF-1 is a 70-amino-acid hormone made mainly in the liver in response to growth hormone (see the main IGF-1 page for its biology). IGF-1 DES is the same protein with the first three amino acids removed from the starting end of the chain (the N-terminus). Nothing else is changed.
Three research groups found it as a natural molecule:
- Human fetal and adult brain. One group isolated a variant IGF-1 with a shortened N-terminus from fetal brain tissue and then from adult brain (Sara et al., PNAS 1986; Carlsson-Skwirut et al., FEBS Lett 1986).
- Bovine colostrum. An Australian CSIRO group purified it from cow colostrum, sequenced it, and found it lacked the N-terminal tripeptide glycine–proline–glutamate (Francis et al., Biochem J 1988).
- Pig uterus. It has also been isolated from porcine uterus (Ballard et al., Int J Biochem Cell Biol 1996).
It probably forms when an enzyme clips IGF-1 after it has been made. Rat serum contains an acid protease that converts intact IGF-1 into des(1-3)IGF-I, with optimal activity at pH 5.5 (Yamamoto & Murphy, Endocrinology 1994). In pooled urine from healthy adults, about 35% of IGF-1 was in N-terminally truncated forms (Yamamoto & Murphy, JCEM 1995).
The researchers also made it synthetically and in genetically engineered cells. Recombinant des(1-3)IGF-I made in hamster ovary cells was as potent as the naturally purified peptide (McKinnon et al., J Mol Endocrinol 1991).
Why removing three amino acids matters
Most IGF-1 in the body is held by IGF binding proteins (IGFBPs). These proteins carry IGF-1 in blood and, in tissues, limit how much of it reaches the IGF-1 receptor. The glutamate at position 3 is essential for IGF-1 to bind them (Ballard et al., Int J Biochem Cell Biol 1996). Remove it, and the binding proteins largely lose their grip.
The Adelaide group tested this directly by making IGF-1 analogues shortened by one to five amino acids (Bagley et al., Biochem J 1989). In rat L6 muscle cells:
| Peptide | Half-maximal dose for protein synthesis | Dose for 50% competition at the receptor |
|---|---|---|
| IGF-1 (full length) | 13 ng/mL | 20 ng/mL |
| des(1)IGF-1 (1 removed) | 10 ng/mL | 20 ng/mL |
| des(1-2)IGF-1 (2 removed) | 13 ng/mL | 20 ng/mL |
| des(1-3)IGF-1 (3 removed) | 1.5 ng/mL | 14 ng/mL |
| des(1-4)IGF-1 (4 removed) | 5.1 ng/mL | 40 ng/mL |
| des(1-5)IGF-1 (5 removed) | 1200 ng/mL | over 1000 ng/mL |
Lower numbers mean higher potency. Removing three amino acids left receptor binding about the same but sharply increased potency (1.5 vs 13 ng/mL). Binding proteins secreted by the muscle cells, and one purified from kidney cells, bound the three longer peptides at least 60-fold better than the three shorter ones. Removing a fifth amino acid nearly abolished activity.
Earlier studies reached the same conclusion. IGF-1 DES was about 7 times more potent than IGF-1 in the protein synthesis assay without binding the receptor any better (Ballard et al., BBRC 1987). A purified binding protein had markedly reduced affinity for it, which the authors said explained the extra potency (Szabo et al., BBRC 1988).
How it differs from the other IGF-1 products
| Product | What was changed | Status |
|---|---|---|
| IGF-1 / mecasermin | Nothing; identical to human IGF-1 | FDA-approved (Increlex) for severe primary IGF-1 deficiency in children |
| IGF-1 DES | First three amino acids removed | Never approved; research chemical |
| IGF-1 LR3 | Position 3 changed to arginine and an extension peptide added to the start | Never approved; research chemical |
LR3 and DES were designed or selected for the same reason: both bind IGF binding proteins poorly. In ligand-blotting tests of plasma from five species, IGF-1 bound the binding proteins much more than IGF-1 DES, which in turn bound more than LR3 (Lord et al., J Endocrinol 1994).
How it behaves in the body
No pharmacokinetic study of IGF-1 DES has been published in humans. The best data come from a tracer study in rats given labeled peptides into a vein (Ballard et al., J Endocrinol 1991):
| Measure in rats | IGF-1 | IGF-1 DES |
|---|---|---|
| Total plasma clearance | 1.20 mL/min/kg | 4.59 mL/min/kg |
| Steady-state volume of distribution | 167 mL/kg | 461 mL/kg |
| Binding to plasma proteins | About half bound in rat plasma in vitro | Essentially none in vitro; most stayed free after injection |
Because it is not held in blood by binding proteins, IGF-1 DES leaves the bloodstream faster and spreads further into tissues. More of it reached the adrenals, brain, skin, stomach and gut than IGF-1. The authors proposed that rapid clearance and greater tissue access could make such analogues more potent in the body, not less.
Two caveats limit how far the rat data carry over to people:
- Rats are an extreme case. The analogues that barely bound in rat plasma bound significantly in plasma from sheep, humans, pigs and chickens (Lord et al., J Endocrinol 1994). In mice, labeled des(1-3)IGF-I was found mainly in the large 150 kDa complex in serum (Sun et al., Cancer Res 1997).
- No published half-life. We found no primary source giving a blood half-life for IGF-1 DES in any species, so the short half-lives often quoted online cannot be verified.
Anti-doping labs can detect it. After a single intramuscular injection of 100 µg/kg in rats, unchanged des(1-3)IGF-I was still detectable in blood 24 hours later (Mongongu et al., Drug Test Anal 2021).
Regulatory status
IGF-1 DES has never been approved by the FDA or any other regulator. French anti-doping researchers state that IGF-1 analogues such as LR3, DES and R3 were never approved for human use but are readily available as black-market products for bodybuilding (Mongongu et al., Drug Test Anal 2021). In a 1996 review, its developers wrote that clinical uses had not yet been evaluated (Ballard et al., Int J Biochem Cell Biol 1996). We found no later clinical trial.
It is a peptide, not an anabolic steroid, and is not named on the US Schedule III list of controlled substances (21 CFR 1308.13).
What the research shows
All findings below come from cell culture or animals. None has been confirmed in people.
Growth and muscle protein in rats
The CSIRO group in Adelaide ran a series of rat studies using small pumps implanted under the skin that release peptide continuously for 7 days. Rats were made catabolic (breaking down body protein) in several ways:
| Rat model | Main finding for IGF-1 DES | Source |
|---|---|---|
| Low-protein diet | At 1.2 mg/kg/day, improved nitrogen balance (after adjusting for intake) and raised muscle protein synthesis by 21%; kidney weight rose 16% | Tomas et al., J Endocrinol 1991 |
| Dexamethasone (a steroid that breaks down muscle) | About 2.5 times more potent than IGF-1 at improving body weight and nitrogen retention | Tomas et al., Biochem J 1992 |
| Diabetes (streptozotocin) | 2.5–3 times more potent than IGF-1 at restoring growth; did not reduce sugar in the urine | Tomas et al., Biochem J 1993 |
The gains in the dexamethasone study were partly in the gut. IGF-1 and especially the analogues increased gut weight by up to 45%, and carcass fractions stayed low. The developers described the most selective effects of IGF-1 DES as being in gut tissues (Ballard et al., Int J Biochem Cell Biol 1996).
In the diabetic rats, IGF-1 and the analogues restored growth but did not correct other insulin-dependent processes in liver, muscle and fat, unlike insulin itself.
Blood sugar in pigs and monkeys
Like IGF-1, IGF-1 DES lowers blood glucose. A study gave single intravenous doses to marmoset monkeys (42–270 µg/kg) and pigs (20 and 50 µg/kg) (Tomas et al., J Endocrinol 1997):
- The analogues were 2–3 times more potent than IGF-1 at lowering glucose, and IGF-1 DES was the most potent of all those tested.
- Glucose stayed low much longer. For the analogues, total glucose lowering over 4 hours was about 4–8 times greater than with IGF-1.
- This happened even though the analogues are cleared from blood faster.
Brain and nerve cells
Because it was first found in brain, IGF-1 DES has been studied as a nerve growth factor. In rat cell culture it improved survival of dopamine-producing neurons (Beck et al., Neuroscience 1993). When injected into the brain of adult rats after a hypoxic-ischemic injury, however, IGF-1 DES did not significantly reduce nerve cell loss (there was only a trend at the highest dose), while full-length IGF-1 did (Guan et al., Endocrinology 1996). The authors suggested binding proteins help target IGF-1 to the injured area.
The cut-off tripeptide
The three amino acids removed from IGF-1, glycine–proline–glutamate (GPE), turned out to be active on their own in rat brain tissue (Sara et al., BBRC 1989). A synthetic analogue of GPE, trofinetide, is now an approved medicine. It improved symptoms over placebo in a 12-week phase 3 trial in 187 females with Rett syndrome, with diarrhea in 80.6% versus 19.1% on placebo (Neul et al., Nat Med 2023). The FDA approved it as Daybue in 2023 for Rett syndrome in patients 2 years and older (Daybue label). This is a separate drug: trofinetide is not IGF-1 DES, and its approval says nothing about IGF-1 DES.
Side effects and risks
No human safety data exist for IGF-1 DES. The risks below come from its known biology and from what is documented for full-length IGF-1.
Hypoglycemia
Low blood sugar is the first warning on the label of approved IGF-1 (mecasermin) and affected 42% of treated children in the label’s trials (Increlex label). In pigs and monkeys, IGF-1 DES lowered glucose more potently and for longer than IGF-1 (Tomas et al., J Endocrinol 1997). The binding proteins that IGF-1 DES escapes are part of what normally buffers IGF-1’s insulin-like effect. In the first human IGF-1 study, hypoglycemia followed a surge of free, unbound IGF-1 (Guler et al., NEJM 1987).
Effects on organs and growth of other tissues
In rats, IGF-1 DES increased kidney weight by 16% in 7 days (Tomas et al., J Endocrinol 1991) and, with IGF-1, enlarged the gut by up to 45% (Tomas et al., Biochem J 1992). Whether similar effects occur in people is unknown.
Cancer
IGF-1 stimulates cell division, and its receptor is overexpressed in many tumors (Sun et al., Cancer Res 1997). The Increlex (mecasermin) label lists active or past cancer as a contraindication and reports tumors more often at above-recommended doses. Whether the greater potency of IGF-1 DES in cell culture means greater cancer risk has never been studied. See the IGF-1 page for the human cancer data.
Product quality
Black-market IGF-1 analogue products show “abundant signs” of lower-quality, oxidized peptide forms (Mongongu et al., Drug Test Anal 2021). Research chemicals are not regulated for identity, dose or sterility.
Legal status and use outside medicine
The WADA 2026 Prohibited List bans “Insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues” at all times under S2.3. IGF-1 DES is covered as an analogue.
Anti-doping labs have published mass-spectrometry methods that tell synthetic analogues apart from the body’s own IGF-1. A German method detects IGF-1 DES, LR3 and R3 and their breakdown products in human plasma down to 0.5 ng/mL (Thomas et al., Growth Horm IGF Res 2017). A French method detected IGF-1 DES in rats for 24 hours after a single injection (Mongongu et al., Drug Test Anal 2021).
Key takeaways
- A natural, shortened IGF-1. IGF-1 DES is human IGF-1 missing its first three amino acids, found in human brain in 1986 and cow colostrum in 1988.
- More potent in the lab because it escapes binding proteins. In rat muscle cells it was about 7–10 times more potent than IGF-1, with similar receptor binding.
- Faster clearance, wider spread. In rats it was cleared from blood much faster than IGF-1 and reached more tissues; no half-life has been published for any species.
- Animal data only. Rat studies showed better growth and nitrogen balance than IGF-1, partly through gut and kidney growth. No controlled human trial exists.
- Stronger, longer hypoglycemia. In pigs and monkeys it lowered blood sugar more and for longer than IGF-1.
- Never approved and banned in sport. It is a research chemical, prohibited at all times by WADA, and detectable by anti-doping labs.
Sources
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- World Anti-Doping Agency. 2026 Prohibited List. WADA 2026 Prohibited List.
- US Code of Federal Regulations. 21 CFR 1308.13, Schedule III. 21 CFR 1308.13.